‘Focusing and Unfocusing’—Cognitive, Evaluative, and Emotional Dynamics in the Relationship with Human Embryos among ART Beneficiaries

This article uses data gathered from a study conducted in Portugal to examine the (plural and composite) conceptions that doctors, embryologists, and beneficiaries of Assisted Reproductive Technology (ART) have of the in vitro human embryo. Taking the sociology of engagements, developed by Thévenot, as its theoretical lens, the article draws on a total of 69 interviews with ART patients to analyse the plurality of fluid meanings produced about this biological entity, whose status is neither static nor universal. ART beneficiaries are likely to produce plural conceptions of the lab-generated embryo within the framework of different regimes of engagement, understood as cognitive and evaluative formats. These various pragmatic regimes, in turn, entail distinct emotional investments. When speaking about their relationship with embryos, beneficiaries therefore express plural emotional experiences, which are articulated using terms such as affection, love, detachment, loss, frustration, hope, mourning, and anguish. Using the theoretical framework of the sociology of engagements, we propose an approach that enables us to produce a detailed record of the connections between the cognitive, evaluative, and emotional dimensions in beneficiaries’ relationship with—and decision-making processes about—the embryos, accounting for the plasticity of emotional states linked to the (re)configuration of attributed meanings.

Functional impact and targetability of PI3KCA, GNAS, and PTEN mutations in a spindle cell rhabdomyosarcoma with MYOD1 L122R mutation

Spindle cell/sclerosing rhabdomyosarcoma (ssRMS) is a rare subtype of rhabdomyosarcoma, commonly harboring a gain-of-function L122R mutation in the muscle-specific master transcription factor MYOD1. MYOD1-mutated ssRMS is almost invariably fatal, and development of novel therapeutic approaches based on the biology of the disease is urgently needed. MYOD1 L122R affects the DNA-binding domain and is believed to confer MYC-like properties to MYOD1, driving oncogenesis. Moreover, the majority of the MYOD1-mutated ssRMS harbor additional alterations activating the PI3K/AKT pathway. It is postulated that the PI3K/AKT pathway cooperates with MYOD1 L122R. To address this biological entity, we established and characterized a new patient-derived ssRMS cell line OHSU-SARC001, harboring MYOD1 L122R as well as alterations in PTEN, PIK3CA, and GNAS. We explored the functional impact of these aberrations on oncogenic signaling with gain-of-function experiments in C2C12 murine muscle lineage cells. These data reveal that PIK3CAI459_T462del, the novel PIK3CA variant discovered in this patient specimen, is a constitutively active kinase, albeit to a lesser extent than PI3KCAE545K, a hotspot oncogenic mutation. Furthermore, we examined the effectiveness of molecularly targeted PI3K/AKT/mTOR and RAS/MAPK inhibitors to block oncogenic signaling and suppress the growth of OHSU-SARC001 cells. Dual PI3K/mTOR (LY3023414, bimiralisib) and AKT inhibitors (ipatasertib, afuresertib) induced dose-dependent reductions in cell growth. However, mTOR-selective inhibitors (everolimus, rapamycin) alone did not exert cytotoxic effects. The MEK1/2 inhibitor trametinib did not impact proliferation even at the highest doses tested. Our data suggest that molecularly targeted strategies may be effective in PI3K/AKT/mTOR-activated ssRMS. Taken together, these data highlight the importance of utilizing patient-derived models to assess molecularly targetable treatments and their potential as future treatment options.

Reconstitution and Transmission of Gut Microbiomes and Their Genes between Generations

Microbiomes are transmitted between generations by a variety of different vertical and/or horizontal modes, including vegetative reproduction (vertical), via female germ cells (vertical), coprophagy and regurgitation (vertical and horizontal), physical contact starting at birth (vertical and horizontal), breast-feeding (vertical), and via the environment (horizontal). Analyses of vertical transmission can result in false negatives (failure to detect rare microbes) and false positives (strain variants). In humans, offspring receive most of their initial gut microbiota vertically from mothers during birth, via breast-feeding and close contact. Horizontal transmission is common in marine organisms and involves selectivity in determining which environmental microbes can colonize the organism’s microbiome. The following arguments are put forth concerning accurate microbial transmission: First, the transmission may be of functions, not necessarily of species; second, horizontal transmission may be as accurate as vertical transmission; third, detection techniques may fail to detect rare microbes; lastly, microbiomes develop and reach maturity with their hosts. In spite of the great variation in means of transmission discussed in this paper, microbiomes and their functions are transferred from one generation of holobionts to the next with fidelity. This provides a strong basis for each holobiont to be considered a unique biological entity and a level of selection in evolution, largely maintaining the uniqueness of the entity and conserving the species from one generation to the next.

Green Synthesis of Gold Nanoparticles: A Novel, Environment-Friendly, Economic, Safe Approach

Nanoparticles can be synthesised using a variety of methods. These approaches, on the other hand, are connected with the development of undesired byproducts that are both harmful and expensive. As a result, several attempts are being undertaken to develop unique, cost-effective, safe, and dependable "green" techniques for producing desirable nanoparticles. To develop a novel, environment-friendly, economic, safe approach to the synthesis of gold nanoparticles via the biological entity. Addition of aqueous gold chloride solution to the microwave-exposed aqueous extracellular Cassia tora leaf extract yielded poly shaped gold nanoparticles. The UV-vis. spectroscopic investigations are led to notice and affirm the formation of nanoparticles. FTIR studies are performed to affirm the role of a biomolecule in stabilizing the nanoparticles. X-beam diffraction study is utilized to affirm the crystalline nature of nanoparticles. The elemental characterization of the samples is regulated by EDX studies. The size and morphology of the synthesized nanoparticles are explored using HR-TEM analysis and FESEM. It is seen that the flavonoids which are separated during microwave warming of extracellular solution of the cassia tora leaves are liable for the biosynthesis of gold nanoparticles. The nanoparticle was noted to be well dispersed and polyshaped with a 20-60 nm range. The leaf extract based preparation of AuNP is more gainful since leaf is used instead of microorganism as many of the issues like pathogenicity, procedural maintenance of hygiene of cell culture and labor efforts can be overcome. The presence of flavonoids in the leaf was discovered by the examination of produced nanoparticles, suggesting that they may have fulfilled both reduction and stabilisation activities. The presented approach can be inferred to be cost-effective, environmentally friendly, and capable of manufacturing nanoparticles with desired physical and pharmacological properties.

Evidence of the Physical Interaction between Rpl22 and the Transposable Element Doc5, a Heterochromatic Transposon of Drosophila melanogaster

Chromatin is a highly dynamic biological entity that allows for both the control of gene expression and the stabilization of chromosomal domains. Given the high degree of plasticity observed in model and non-model organisms, it is not surprising that new chromatin components are frequently described. In this work, we tested the hypothesis that the remnants of the Doc5 transposable element, which retains a heterochromatin insertion pattern in the melanogaster species complex, can be bound by chromatin proteins, and thus be involved in the organization of heterochromatic domains. Using the Yeast One Hybrid approach, we found Rpl22 as a potential interacting protein of Doc5. We further tested in vitro the observed interaction through Electrophoretic Mobility Shift Assay, uncovering that the N-terminal portion of the protein is sufficient to interact with Doc5. However, in situ localization of the native protein failed to detect Rpl22 association with chromatin. The results obtained are discussed in the light of the current knowledge on the extra-ribosomal role of ribosomal protein in eukaryotes, which suggests a possible role of Rpl22 in the determination of the heterochromatin in Drosophila.

Effects of a Self-Regulated Training Program on the Repeated Power in Female College Handball Players: An Intervention Study

Several resistance training programs using conventional methodologies have been implemented with the purpose of improving the ability to perform power actions in handball, especially during the competitive season. In contrast, methodologies based on a contemporary perspective, which considers the human being as a self-regulating biological entity, and designed specifically for female college players, are scarce. The aim of this research was to investigate the effects of an eight-week resistance training program, in which the athletes were able to control the loads according to their self-perceived effort and rest on their repeated shuttle sprint and jump ability. The sample was composed of 16 female players of a handball team from the faculty of physics and mathematics sciences of a Chilean university. The RSSJA test was used to evaluate players’ conditions pre- and post-training program, and the self-perceived effort scale called OMNI-RES was used for the prediction and control of loads. Results indicated that, after the application of an eight-week resistance training program, significant improvements p ≤ 0.05 on the jump height (pre: 1836.4 W; average post: 2088.9 W) and running speed (average pre: 3.2 m/s; average post: 4.0 m/s) were obtained, as well as a significant reduction in the loss of power and speed between each set of the applied test.

Mycobacteriophages to Treat Tuberculosis: Dream or Delusion?

Rates of antimicrobial resistance are increasing globally while the pipeline of new antibiotics is drying up, putting patients with disease caused by drug-resistant bacteria at increased risk of complications and death. The growing costs for diagnosis and management of drug resistance threaten tuberculosis control where the disease is endemic and resources limited. Bacteriophages are viruses that attack bacteria. Phage preparations served as anti-infective agents long before antibiotics were discovered. Though small in size, phages are the most abundant and diverse biological entity on earth. Phages have co-evolved with their hosts and possess all the tools needed to infect and kill bacteria, independent of drug resistance. Modern biotechnology has improved our understanding of the biology of phages and their possible uses. Phage preparations are available to treat meat, fruit, vegetables, and dairy products against parasites or to prevent contamination with human pathogens, such as <i>Listeria monocytogenes, Escherichia coli</i>, or <i>Staphylococcus aureus</i>. Such phage-treated products are considered fit for human consumption. A number of recent case reports describe in great detail the successful treatment of highly drug-resistant infections with individualized phage preparations. Formal clinical trials with standardized products are slowly emerging. With its highly conserved genome and relative paucity of natural phage defence mechanisms <i>Mycobacterium tuberculosis</i> appears to be a suitable target for phage treatment. A phage cocktail with diverse and strictly lytic phages that kill all lineages of <i>M. tuberculosis,</i> and can be propagated on <i>Mycobacterium smegmatis</i>, has been assembled and is available for the evaluation of optimal dosage and suitable routes of administration for tuberculosis in humans. Phage treatment can be expected to be safe and active on extracellular organisms, but phage penetration to intracellular and granulomatous environments as well as synergistic effects with antibiotics are important questions to address during further evaluation.

Characterization of N4-like Pseudomonas Phage vB_Pae-PA14 Isolated from Seawater Sampled in Thailand

Bacteriophage, a predator virus of bacteria, is an abundant biological entity in the biosphere. With ultimate applications in medicine and biotechnology, new phages are extensively being isolated and characterized. The objective of the present study was to characterize lytic bacteriophage vB_Pae-PA14 infecting Pseudomonas aeruginosa ATCC 27853 that was isolated from seawater in Thailand. vB_Pae-PA14 was subjected to whole genome phylogenetic analysis, host range test, biofilm test and characterization. Results showed that the phage belonged to a group of N4-like viruses, could infect P. aeruginosa isolates including carbapenem-resistant P. aeruginosa. The burst size of vB_Pae-PA14 was 86 plaque-forming unit/infected cells. Also, the phage showed a greater ability to control planktonic P. aeruginosa cells than the biofilm cells. Phage could withstand physical stresses especially the high salt concentration. In brief, lytic bacteriophage vB_Pae-PA14 infecting P. aeruginosa was isolated and characterized, which might be useful in further bacteriophage lytic applications.

Streptococcus pneumoniae: a Plethora of Temperate Bacteriophages With a Role in Host Genome Rearrangement

Bacteriophages (phages) are viruses that infect bacteria. They are the most abundant biological entity on Earth (current estimates suggest there to be perhaps 1031 particles) and are found nearly everywhere. Temperate phages can integrate into the chromosome of their host, and prophages have been found in abundance in sequenced bacterial genomes. Prophages may modulate the virulence of their host in different ways, e.g., by the secretion of phage-encoded toxins or by mediating bacterial infectivity. Some 70% of Streptococcus pneumoniae (the pneumococcus)—a frequent cause of otitis media, pneumonia, bacteremia and meningitis—isolates harbor one or more prophages. In the present study, over 4000 S. pneumoniae genomes were examined for the presence of prophages, and nearly 90% were found to contain at least one prophage, either defective (47%) or present in full (43%). More than 7000 complete putative integrases, either of the tyrosine (6243) or serine (957) families, and 1210 full-sized endolysins (among them 1180 enzymes corresponding to 318 amino acid-long N-acetylmuramoyl-L-alanine amidases [LytAPPH]) were found. Based on their integration site, 26 different pneumococcal prophage groups were documented. Prophages coding for tRNAs, putative virulence factors and different methyltransferases were also detected. The members of one group of diverse prophages (PPH090) were found to integrate into the 3’ end of the host lytASpn gene encoding the major S. pneumoniae autolysin without disrupting it. The great similarity of the lytASpnand lytAPPH genes (85–92% identity) allowed them to recombine, via an apparent integrase-independent mechanism, to produce different DNA rearrangements within the pneumococcal chromosome. This study provides a complete dataset that can be used to further analyze pneumococcal prophages, their evolutionary relationships, and their role in the pathogenesis of pneumococcal disease.

An assessment of the taxonomic validity of three species of marsupial frogs (Anura: Hemiphractidae: Gastrotheca) from the Yungas of Bolivia based on external morphology and cranial osteology

The genus Gastrotheca (Anura: Hemiphractidae) is a group of marsupial frogs particularly diverse in Andean regions. Several taxonomic studies of this genus have been conducted in the humid cloud forests—or Yungas—of the Andean eastern slopes of central Bolivia (departments of Cochabamba and Santa Cruz). Yet, the distinction among three species that occur sympatrically in these forests, G. lauzuricae (proposed as a junior synonym of G. coeruleomaculatus in 2015), G. piperata, and G. splendens, remains unclear since the morphological characters that purportedly support their differentiation are variable and partly shared among them. We have carried out external morphological studies, including multivariate morphometric analyses, to assess how they support the taxonomic status of these three species. We also evaluated characters of the cranial osteology of a sample of six individuals using micro CT-scanning. Principal component and linear discriminant analyses resulted in a great overlap among the putative species. Cranial osteological comparisons did not reveal highly significant differences among them, but suggested that different degrees of hyperossification could be related to the developmental state of individuals. Our results indicate that most morphological and osteological reported differences between the three species likely represent intraspecific variation. Thus, we propose that the three nominal species belong to a single biological entity, for which the name Gastrotheca splendens (Schmidt, 1857) has priority. We also restrict the name Gastrotheca coeruleomaculatus (Werner, 1899) to externally similar congeneric populations from the Yungas forests of department of La Paz, but highlighting the need of a detailed evaluation of their taxonomic identity.